Olfactory receptors modulate physiological processes in human airway smooth muscle cells
Pathophysiological mechanisms in human airway smooth muscle cells (HASMCs) significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflam...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-08-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00339/full |
| _version_ | 1818874655919833088 |
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| author | Benjamin Kalbe Jürgen Knobloch Viola Maria Schulz Christine Wecker Marian Schlimm Paul Scholz Fabian Jansen Erich Stoelben Stathis Philippou Erich Hecker Hermann Luebbert Andrea Koch Hanns Hatt Sabrina Osterloh |
| author_facet | Benjamin Kalbe Jürgen Knobloch Viola Maria Schulz Christine Wecker Marian Schlimm Paul Scholz Fabian Jansen Erich Stoelben Stathis Philippou Erich Hecker Hermann Luebbert Andrea Koch Hanns Hatt Sabrina Osterloh |
| author_sort | Benjamin Kalbe |
| collection | DOAJ |
| description | Pathophysiological mechanisms in human airway smooth muscle cells (HASMCs) significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflammatory proteins. To develop therapeutic strategies, key pathological mechanisms and putative clinical targets need to be identified. In the present study, we demonstrated that the human olfactory receptors (ORs) OR1D2 and OR2AG1 are expressed at the RNA and protein levels in HASMCs. Using fluorometric calcium imaging, specific agonists for OR2AG1 and OR1D2 were identified to trigger transient Ca2+ increases in HASMCs via a cAMP-dependent signal transduction cascade. Furthermore, the activation of OR2AG1 via amyl butyrate inhibited the histamine-induced contraction of HASMCs, whereas the stimulation of OR1D2 with bourgeonal led to an increase in cell contractility. In addition, OR1D2 activation induced the secretion of IL-8 and GM-CSF. Both effects were inhibited by the specific OR1D2 antagonist undecanal. We herein provide the first evidence to show that ORs are functionally expressed in HASMCs and regulate pathophysiological processes. Therefore, ORs might be new therapeutic targets for these diseases, and blocking ORs could be an auspicious strategy for the treatment of early-stage chronic inflammatory lung diseases. |
| first_indexed | 2024-12-19T13:14:04Z |
| format | Article |
| id | doaj.art-c0daf725a43a40bc87da6be3d75f389e |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T13:14:04Z |
| publishDate | 2016-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-c0daf725a43a40bc87da6be3d75f389e2022-12-21T20:19:52ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-08-01710.3389/fphys.2016.00339197867Olfactory receptors modulate physiological processes in human airway smooth muscle cellsBenjamin Kalbe0Jürgen Knobloch1Viola Maria Schulz2Christine Wecker3Marian Schlimm4Paul Scholz5Fabian Jansen6Erich Stoelben7Stathis Philippou8Erich Hecker9Hermann Luebbert10Andrea Koch11Hanns Hatt12Sabrina Osterloh13Ruhr-University BochumUniversity Hospital BergmannsheilRuhr-University BochumRuhr-University BochumRuhr-University BochumRuhr-University BochumRuhr-University BochumLungenklinik MerheimAugusta-Kranken-AnstaltEvangelisches Krankenhaus HerneRuhr-University BochumUniversity Hospital BergmannsheilRuhr-University BochumRuhr-University BochumPathophysiological mechanisms in human airway smooth muscle cells (HASMCs) significantly contribute to the progression of chronic inflammatory airway diseases with limited therapeutic options, such as severe asthma and COPD. These abnormalities include the contractility and hyperproduction of inflammatory proteins. To develop therapeutic strategies, key pathological mechanisms and putative clinical targets need to be identified. In the present study, we demonstrated that the human olfactory receptors (ORs) OR1D2 and OR2AG1 are expressed at the RNA and protein levels in HASMCs. Using fluorometric calcium imaging, specific agonists for OR2AG1 and OR1D2 were identified to trigger transient Ca2+ increases in HASMCs via a cAMP-dependent signal transduction cascade. Furthermore, the activation of OR2AG1 via amyl butyrate inhibited the histamine-induced contraction of HASMCs, whereas the stimulation of OR1D2 with bourgeonal led to an increase in cell contractility. In addition, OR1D2 activation induced the secretion of IL-8 and GM-CSF. Both effects were inhibited by the specific OR1D2 antagonist undecanal. We herein provide the first evidence to show that ORs are functionally expressed in HASMCs and regulate pathophysiological processes. Therefore, ORs might be new therapeutic targets for these diseases, and blocking ORs could be an auspicious strategy for the treatment of early-stage chronic inflammatory lung diseases.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00339/fullCytokinessignalingContractionsmooth muscle cellsolfactory receptor |
| spellingShingle | Benjamin Kalbe Jürgen Knobloch Viola Maria Schulz Christine Wecker Marian Schlimm Paul Scholz Fabian Jansen Erich Stoelben Stathis Philippou Erich Hecker Hermann Luebbert Andrea Koch Hanns Hatt Sabrina Osterloh Olfactory receptors modulate physiological processes in human airway smooth muscle cells Frontiers in Physiology Cytokines signaling Contraction smooth muscle cells olfactory receptor |
| title | Olfactory receptors modulate physiological processes in human airway smooth muscle cells |
| title_full | Olfactory receptors modulate physiological processes in human airway smooth muscle cells |
| title_fullStr | Olfactory receptors modulate physiological processes in human airway smooth muscle cells |
| title_full_unstemmed | Olfactory receptors modulate physiological processes in human airway smooth muscle cells |
| title_short | Olfactory receptors modulate physiological processes in human airway smooth muscle cells |
| title_sort | olfactory receptors modulate physiological processes in human airway smooth muscle cells |
| topic | Cytokines signaling Contraction smooth muscle cells olfactory receptor |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00339/full |
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